Cargando…

Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss

The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platel...

Descripción completa

Detalles Bibliográficos
Autores principales: Holers, V. Michael, Girardi, Guillermina, Mo, Lian, Guthridge, Joel M., Molina, Hector, Pierangeli, Silvia S., Espinola, Ricardo, Xiaowei, Liu E., Mao, Dailing, Vialpando, Christopher G., Salmon, Jane E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193604/
https://www.ncbi.nlm.nih.gov/pubmed/11805148
http://dx.doi.org/10.1084/jem.200116116
_version_ 1782147510078275584
author Holers, V. Michael
Girardi, Guillermina
Mo, Lian
Guthridge, Joel M.
Molina, Hector
Pierangeli, Silvia S.
Espinola, Ricardo
Xiaowei, Liu E.
Mao, Dailing
Vialpando, Christopher G.
Salmon, Jane E.
author_facet Holers, V. Michael
Girardi, Guillermina
Mo, Lian
Guthridge, Joel M.
Molina, Hector
Pierangeli, Silvia S.
Espinola, Ricardo
Xiaowei, Liu E.
Mao, Dailing
Vialpando, Christopher G.
Salmon, Jane E.
author_sort Holers, V. Michael
collection PubMed
description The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1–related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation.
format Text
id pubmed-2193604
institution National Center for Biotechnology Information
language English
publishDate 2002
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21936042008-04-14 Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss Holers, V. Michael Girardi, Guillermina Mo, Lian Guthridge, Joel M. Molina, Hector Pierangeli, Silvia S. Espinola, Ricardo Xiaowei, Liu E. Mao, Dailing Vialpando, Christopher G. Salmon, Jane E. J Exp Med Original Article The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1–related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation. The Rockefeller University Press 2002-01-21 /pmc/articles/PMC2193604/ /pubmed/11805148 http://dx.doi.org/10.1084/jem.200116116 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Holers, V. Michael
Girardi, Guillermina
Mo, Lian
Guthridge, Joel M.
Molina, Hector
Pierangeli, Silvia S.
Espinola, Ricardo
Xiaowei, Liu E.
Mao, Dailing
Vialpando, Christopher G.
Salmon, Jane E.
Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title_full Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title_fullStr Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title_full_unstemmed Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title_short Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
title_sort complement c3 activation is required for antiphospholipid antibody-induced fetal loss
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193604/
https://www.ncbi.nlm.nih.gov/pubmed/11805148
http://dx.doi.org/10.1084/jem.200116116
work_keys_str_mv AT holersvmichael complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT girardiguillermina complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT molian complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT guthridgejoelm complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT molinahector complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT pierangelisilvias complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT espinolaricardo complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT xiaoweiliue complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT maodailing complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT vialpandochristopherg complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss
AT salmonjanee complementc3activationisrequiredforantiphospholipidantibodyinducedfetalloss